Prognostic factors in Crohn's disease: a systematic review.

BACKGROUND: The natural history of Crohn's disease is associated with several factors that affect the prognostic of the patients. AIMS: To determine the most prognostic factors in Crohn's disease, based on a systematic review. METHODS: Literature review. RESULTS: The most important factors to consider in patients with Crohn's disease are the need for immunosuppressive therapy, the need for intestinal resection and disabling disease. Prognostic factors for these events are ileal involvement, perianal disease and initial treatment by corticosteroid. Other factors such young age, CRP level and smoking status, has not been found in all population-based studies. Protective role of anti-TNF drugs is strongly suggested but need to be confirmed in further studies. CONCLUSION: In a selected subgroup of patients with Crohn's disease characterized by the presence of these prognostic markers, the "topdown" strategy can be proposed.

Unbalanced bone remodeling in Tunisian patients with inflammatory bowel diseases.

BACKGROUND: Bone loss is an ignored complication in inflammatory bowel diseases. Its underling mechanisms are not fully elucidated. OBJECTIVES: To investigate bone turnover in patients with inflammatory bowel diseases. METHODS: The study included 67 patients with inflammatory bowel diseases and 54 age- and sex-matched healthy subjects. Urinary degradation products of C-terminal telopeptide of type I collagen, serum osteocalcin, parathyroid hormone, 25 hydroxy vitamin D and interleukin-6 were assessed. Bone mineral density was measured by dual energy-X-ray absorptiometry and osteoporosis was defined as T score < -2.5 SD. RESULTS: Patients showed significantly higher levels of C-terminal telopeptide of type I collagen and interleukin-6 and lower levels of 25 hydroxy vitamin D. Serum osteocalcin and parathyroid hormone were in normal range. In multivariate analysis, urinary degradation products of C-terminal telopeptide of type I collagen were associated with disease activity (p=0.04) and osteocalcin was associated with parathyroid hormone (p=0.04). Urinary degradation products of Cterminal telopeptide of type I collagen and interleukin-6 were significantly increased in inflammatory bowel disease patients with osteoporosis. No association was found between osteoporosis and serum osteocalcin, parathyroid hormone and 25 hydroxy vitamin D. CONCLUSION: Bone resorption rate is increased and is associated with osteoporosis in inflammatory bowel disease patients. Inflammation, malnutrition, and hypovitaminosis D may contribute to the bone loss.

Circulating antimyenteric autoantibodies in Tunisian patients with idiopathic achalasia.

The physiopathology of idiopathic achalasia is still unknown. The description of circulating antimyenteric autoantibodies (CAA), directed against enteric neurons in sera of patients, suggests an autoimmune process. Recent data showed controversies according to the existence and the significance of CAA. The aims of this study were to investigate whether CAA are detected in Tunisian patients with idiopathic achalasia and to look for associated clinical or manometrical factors with CAA positivity. Twenty-seven patients with idiopathic achalasia and 57 healthy controls were prospectively studied. CAA were assessed by indirect immunofluorescence on intestinal monkey tissue sections. Western blot on primate cerebellum protein extract and dot technique with highly purified recombinant neuronal antigens (Hu, Ri, and Yo) were further used to analyze target antigens of CAA. CAA were significantly increased in achalasia patients compared with controls when considering nuclear or cytoplasmic fluorescence patterns. (33% vs. 12%, P = 0.03 and 48% vs. 23%, P = 0.001 respectively). By immunoblot analysis, CAA did not target neuronal antigens, however 52/53 and 49 kDa bands were consistently detected. CAA positivity was not correlated to specific clinical features. The results are along with previous studies demonstrating high CAA prevalence in achalasia patients. When reviewing technical protocols and interpretation criteria, several discrepancies which could explain controversies between studies were noted.

Brain processing of duodenal and portal glucose sensing.

Peripheral and central glucose sensing play a major role in the regulation of food intake. Peripheral sensing occurs at duodenal and portal levels, although the importance of these sensing sites is still controversial. The present study aimed to compare the respective influence of these sensing pathways on the eating patterns; plasma concentrations of glucose, insulin and glucagon-like peptide-1 (GLP-1); and brain activity in juvenile pigs. In Experiment 1, we characterised the changes in the microstructure as a result of a 30-min meal in eight conscious animals after duodenal or portal glucose infusion in comparison with saline infusion. In Experiment 2, glucose, insulin and GLP-1 plasma concentrations were measured during 2 h after duodenal or portal glucose infusions in four anaesthetised animals. In Experiment 3, single photon emission computed tomography brain imaging was performed in five anaesthetised animals receiving duodenal or portal glucose or saline infusions. Both duodenal and portal glucose decreased the amount of food consumed, as well as the ingestion speed, although this effect appeared earlier with the portal infusion. Significant differences of glucose and GLP-1 plasma concentrations between treatments were found at the moment of brain imaging. Both duodenal and portal glucose infusions activated the dorsolateral prefrontal cortex and primary somatosensory cortex. Only duodenal glucose infusion was able to induce activation of the prepyriform area, orbitofrontal cortex, caudate and putamen, as well as deactivation of the anterior prefrontal cortex and anterior entorhinal cortex, whereas only portal glucose infusion induced a significant activation of the insular cortex. We demonstrated that duodenal and portal glucose infusions led to the modulation of brain areas that are known to regulate eating behaviour, which probably explains the decrease of food intake after both stimulations. These stimulation pathways induced specific systemic and central responses, suggesting that different brain processing matrices are involved.

[Efficacy and safety of Adalimumab in Crohn's disease]. / Indications et résultats de l'adalimumab au cours de la maladie de Crohn.

BACKGROUND: Adalimumab is the first subcutaneously self administered fully human anti-TNFa. AIM: To determine efficacy and safety of Adalimumab therapy in Crohn disease. METHODS: Literature review. RESULTS: Adalimumab has been evaluated for its effect in inducing and maintaining remission and its steroid-sparing effect of refractory Crohn's disease. In addition, it offers a significant treatment option in patients who have lost response to or become intolerant to Infliximab. Results also suggest efficacy of Adalimumab in fistulising Crohn's disease but more studies are needed. Adalimumab was well tolerated and studies show that all anti-TNF inhibitors have similar safety profiles.

Ethyl acetate extract and its major constituent, isorhamnetin 3-O-rutinoside, from Nitraria retusa leaves, promote apoptosis of human myelogenous erythroleukaemia cells.

OBJECTIVE: Fractionation of ethyl acetate extract (EA) obtained from Nitraria retusa leaves was assessed using different methods of chromatography, and isorhamnetin3-O-rutinoside (I3-O-R) was isolated from this extract. Its structure was determined using data obtained from (1) H and (13) C NMR spectra, as well as by various correlation experiments (COSY, HMQC and HMBC). Both EA extract and I3-O-R were investigated for their ability to induce apoptosis in human chronic myelogenous erythroleukaemia cells (K562). MATERIALS AND METHODS: Apoptosis of cells from the K562 line was detected by DNA fragmentation, PARP cleavage and by evaluating activities of caspases 3 and 8. RESULTS: Apoptosis, revealed by DNA fragmentation and PARP cleavage, was observed after 48-h incubation of these human myelogenous erythroleukaemia cells (K562), with the tested products. Likewise, caspase 3 and caspase 8 activities were induced in the presence of the EA extract and I3-O-R after 48 h of incubation. CONCLUSION: Our results strongly suggest the involvement of the extrinsic pathway of apoptosis in cells treated by both the original EA extract and its major component, I3-O-R.

Antimutagenic, antigenotoxic and antioxidant activities of phenolic-enriched extracts from Teucrium ramosissimum: combination with their phytochemical composition.

The evaluation of the mutagenic and antimutagenic actions of extracts obtained from aerial part of Teucrium ramosissimum was assayed using the Salmonella typhimurium assay system. The effect of the same extracts on genotoxicity and SOS response induced by aflatoxin B(1) as well as nitrofurantoin was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. The different extracts showed no mutagenicity when tested with Salmonella typhimurium strains TA100, TA98 and TA1535 either with or without S9 mix. In contrast, our results prove that T. ramosissimum extracts possess antimutagenic effects against sodium azide, aflatoxin B1, benzo[a]pyrene and 4-nitro-o-phenylenediamine. Moreover, the T. ramosissimum tested extracts exhibited no genotoxicity either with or without the external S9 activation mixtures. However, all the extracts significantly decreased the genotoxicity induced by aflatoxin B(1) and nitrofurantoin. The result obtained by the Ames test confirms those of SOS chromotest. Antioxidant capacity of the tested extracts was evaluated using the enzymatic (xanthine/xanthine oxidase assay) and the non enzymatic (NBT/riboflavine, DPPH and ABTS assays) systems. All extracts exhibited high antioxidant activity except the chloroform and the methanol extracts in DPPH and NBT/riboflavine assays respectively. Our results underline the potential of T. ramosissimum to avoid mutations and also its antioxidant potential.

Induction of apoptosis in human lymphoblastoid cells by kaempferol 3-O-ß-isorhamninoside and rhamnocitrin 3-O-ß-isorhamninoside from Rhamnus alaternus L. (Rhamnaceae).

OBJECTIVE: Kaempferol 3-O-ß-isorhamninoside (K3O-ir) and rhamnocitrin 3-O-ß-isorhamninoside (R3O-ir) from Rhamnus alaternus L leaves are investigated for their ability to induce apoptosis in human lymphoblastoid cells. We have attempted to characterize apoptotic pathway activated by these two flavonoids. MATERIAL AND METHODS: Apoptosis of the human TK6 lymphoblastoid cell line was detected by DNA fragmentation, PARP cleavage and by evaluating caspase activity. RESULTS: Apoptosis was observed after 24- and 48-h incubation of the cells with the tested compounds. DNA fragmentation was observed after treatment with flavonoids; this was confirmed by demonstration of PARP cleavage. Caspase-3 and caspase-8 activities were induced by both K3O-ir and R3O-ir flavonoids showing highest activity with compound concentration of 400 µg/ml. CONCLUSION: We have demonstrated that K3O-ir and R3O-ir induce apoptosis in human lymphoblastoid cells by the extrinsic pathway of apoptosis.

Metabolic syndrome is associated with gastroesophageal reflux disease based on a 24-hour ambulatory pH monitoring.

Several studies have focused on the relationship between metabolic syndrome and gastroesophageal reflux disease (GERD). They were based on GERD complications, whereas little is known about the association between metabolic syndrome and objectively measured esophageal acid exposure. The aim of our study was to assess the relationship between metabolic syndrome and GERD based on a 24-hour pH testing. It was a cross-sectional study including 100 consecutive patients who underwent a 24-hour pH-metry monitoring and were assessed for the five metabolic syndrome components as well as for body mass index (BMI). Among the 100 patients, 54 had a pathological acid GERD. The 46 GERD-free patients represented control group. Sex distribution was comparable between both groups but GERD patients were older than controls (44.59 vs. 37.63 years, P= 0.006) and more often obese or with overweight (83.3 vs. 60.9%, P= 0.01). Frequency of metabolic syndrome as a whole entity was higher among patients with GERD than those without GERD (50 vs. 19.56%; P= 0.002) with a crude odds ratio of 4.11 (95% confidence interval: 1.66-10.14). Multivariate regression analysis showed that metabolic syndrome as well as an age ≥ 30 years were independent factors associated to GERD but not BMI and sex. Abnormal waist circumference and fasting glucose level ≥ 100 mg/L were the only independent factors among the five components of metabolic syndrome. Metabolic syndrome but not BMI was an independent factor associated to GERD. These results confirm the hypothesis that central obesity is associated to GERD.

Chemical investigation of different crude extracts from Teucrium ramosissimum leaves. Correlation with their antigenotoxic and antioxidant properties.

The effect of extracts obtained from Teucrium ramosissimum leaves on genotoxicity and SOS response induced by aflatoxin B(1) (0.5 µg/assay) as well as nitrofurantoin (5 µg/assay) was investigated in a bacterial assay system, i.e., the SOS chromotest with Escherichia coli PQ37. The T. ramosissimum tested extracts exhibited no genotoxicity either with or without the external S9 activation mixture. However, all the extracts, particularly the total oligomers flavonoids (TOF) extract significantly decreased the genotoxicity induced by aflatoxin B(1) and nitrofurantoin. Antioxidant capacity of the tested extracts was evaluated using the enzymatic (xanthine/xanthine oxidase assay) (X/XOD) and the non-enzymatic (NBT/Riboflavine assay) systems. TOF extract was the most effective one in inhibiting both xanthine oxidase activity and NBT reduction. Our findings emphasize the potential of T. ramosissimum to prevent mutations and also its antioxidant effect.

Assessment of phenolic content, free-radical-scavenging capacity genotoxic and anti-genotoxic effect of aqueous extract prepared from Moricandia arvensis leaves.

The present study was undertaken to provide a set of data on the safety of an aqueous extract (AQE) from Moricandia arvensis. For this reason, Escherichia coli tested strains PQ35 and PQ37 were used to detect induction of DNA lesions by AQE. The SOS Chromotest showed that AQE induced a marginally genotoxic effect, as expressed by the induction factor (IF) value only with E. coli PQ37 tested strain (IF=1.77 at a dose of 250 microg/assay). The measurement of the anti-genotoxic activity of the AQE was also studied by inhibition of beta-galactosidase induction. A significant anti-genotoxic effect was observed with different tested doses of AQE, which suggests that M. arvensis extract has the potential to protect DNA from the action of nitrofurantoïn (NF) and free radicals generated by hydrogen peroxide (H2O2). In addition to anti-genotoxic activity, AQE showed a free-radical-scavenging capacity towards ABTS+* and DPPH*. Total phenolic content was also evaluated following Folin-Ciocalteu method and results indicated high correlation between total phenol content and anti-genotoxic and antioxidant activities for AQE, but the highest correlation was showed with its capacity to stabilize ABTS+* (R2=0.9944).

Seroprevalence of Helicobacter pylori among Tunisian blood donors (outpatients), symptomatic patients and control subjects.

OBJECTIVES: Helicobacter pylori is a worldwide infection, although little data are available in the Tunisian population. The aims of our study were to detect the prevalence of H. pylori in a blood-donor population (n=250) and in another population of hospital-consulting patients comprising 87 symptomatic patients and 59 controls, and to determine the factors that influence the prevalence. MATERIALS AND METHODS: Study subjects answered a standardized questionnaire, and IgG anti-H. pylori and anti-cag were detected by ELISA. In the second population, culture and cagA polymerase chain reaction were performed. RESULTS: The seroprevalence of H. pylori in blood donors was 64%, and 11% had anti-cag. All patients positive for anti-cag were also positive for anti-H. pylori antibodies. The seroprevalence of H. pylori was 99.3% in the hospital-consulting patients, of whom 55.5% were positive for anti-cag. The difference between the anti-cag and symptomatic patients (66.7%) and controls (39%) was significant. Symptomatic patients had a higher rate of anti-cag (66.7%) compared with the controls (39%) and blood donors (11%). CONCLUSION: H. pylori seroprevalence in blood donors is low (64%) compared with symptomatic patients (99.3%), and anti-cag was statistically associated with symptomatic patients and pathology. Also, some environmental factors were correlated with H. pylori seroprevalence.

Effect of pantoprazole in patients with chronic laryngitis and pharyngitis related to gastroesophageal reflux disease: clinical, proximal, and distal pH monitoring results.

Few studies had evaluated the results of proton pump inhibitors on distal and proximal pH recording using a dual-channel probe. The aim of this study was to determine the clinical and pH-metric effect of treatment with pantoprazole 80 mg for 8 weeks in patients with ear, nose, and throat (ENT) manifestations of gastroesophageal reflux disease associated with pathological proximal acid exposure. We conducted a prospective open study. Patients included had to have chronic pharyngitis or laryngitis, and a pathological gastroesophagopharyngeal reflux. All patients received treatment with pantoprazole 80 mg daily for 8 weeks. One week after the end treatment, patients had a second ENT examination and a 24-hour pH monitoring using dual-channel probe. We included 33 patients (11 men, 22 women). A pathological distal acid reflux was found in 30 patients (91%). After treatment, the improvement of ENT symptoms was found in 51.5% of patients. Normalization of 24-hour proximal esophageal pH monitoring was observed in 22 patients (66%). After treatment, the overall distal acid exposure, the number of distal reflux events, and the number of reflux during more than 5 minutes were significantly decreased (respectively: 19.4% vs 7.2% [P < 0.0001], 62.7 vs 28.4 [P < 0.0001], and 10.4 vs 3.9 [P < 0.0001] ). Similarly, in proximal level, the same parameters were significantly decreased after treatment (respectively: 6.8% vs 1.6% [P < 0.0001], 32.6 vs 8.1 [P < 0.0001], and 3.4 vs 0.6 [P= 0.005] ). Treatment with pantoprazole reduced the frequency and severity of gastroesophagopharyngeal acid reflux in patients with chronic pharyngitis and laryngitis.

Antigenotoxic and antioxidant activities of Pituranthos chloranthus essential oils.

The SOS-chromotest in Escherichia coli is a widely used bacterial genotoxicity assay to test potential carcinogens. The aim of this work is to evaluate the genotoxic and antigenotoxic activities of essential oils obtained from aerial parts of Pituranthos chloranthus. The tested essential oils were not genotoxic towards both E. coli PQ37 and PQ35 strains. These essential oils reduced significantly Nifuroxazide and H(2)O(2)-induced genotoxicity. Essential oils showed a protective effect against damages induced by radicals, obtained from the photolysis of H(2)O(2), on DNA plasmid through free radical scavenging mechanisms. The scavenging capacity of these essential oils was also estimated by evaluating the inhibition of ABTS(+.) radical.

Familial cases of glomerulonephritis complicating Crohn's disease.

A part from nephrolithiasis, renal involvement is rare in the course of Crohn's disease, particularly glomerulonephritis. On the other hand, while onset of Crohn's disease is strongly influenced by environmental and genetic factors, little is known regarding influence of these factors on extra intestinal manifestations. We report a familial case of glomerulonephritis that occurred in a 38-year old woman and her mother, 59 years old with a 7-year and a 37 year history of stenosing ileocolonic disease, respectively. Both of them developed peripheral oedema with nephrotic syndrome during the course of their Crohn's disease while they had no intestinal symptoms and were not receiving any maintenance therapy. Renal function was conserved in the former while the latter developed renal failure and had already small size kidneys on abdominal sonography. Thus, renal biopsy had been performed only in the former patient and had showed membranous glomerulonephritis. Investigations showed no other underlying disease than Crohn's disease. Through this report we emphasis possible genetic influence on extra intestinal manifestations, particularly glomerulonephritis, in Crohn's disease patients.

Antigenotoxic and free radical scavenging activities of extracts from Moricandia arvensis.

This study evaluates genotoxic and antigenotoxic effects of extracts from leaves of Moricandia arvensis, which are used in traditional cooking and medicines. Extracts showed no genotoxicity when tested with the SOS Chromotest using E. coli PQ37 and PQ35 strains, except for the total oligomers flavonoids enriched extract. Petroleum ether and methanol extracts are the most active in reducing nitrofurantoin genotoxicity, whereas methanol and total oligomers flavonoids enriched extracts showed the most important inhibitory effect of H2O2 genotoxicity. In addition, these two extracts showed important free radical scavenging activity toward the DPPH. radical, whereas the chloroform extract exhibited the highest value of TEAC against ABTS+. radical.

Correlation between levels of C-reactive protein and clinical activity in Crohn's disease.

AIMS: To determine the factors associated with an increased C-reactive protein level in Crohn's disease patients and to seek a correlation between the C-reactive protein value and the Crohn's disease activity index. METHODS: We prospectively studied 103 Crohn's disease patients, 76% of whose disease was active at the time of inclusion. C-reactive protein measurement was carried out on all patients. An increased C-reactive protein level was defined as >/=10mg/L. RESULTS: The median C-reactive protein rate was 53.9mg/L (ranging from 1 to 228mg/L). An increased C-reactive protein was found in 77 patients (75%). By univariate analysis, ileocolic localization, severity of the flare, erythrocyte sedimentation rate, leukocyte and platelet count, fibrinogen, albumin, serum calcium and Crohn's disease activity index were found to be associated to elevated C-reactive protein values. By multivariate analysis, independent factors associated with an increased C-reactive protein level were: ileocolic localization (p=0.02; OR [95% CI]: 2.84 [1.25-9.52]) and moderate or severe disease activity (p=0.001; OR [95% CI]: 4.20 [1.92-8.64]). A statistically significant association between the Crohn's disease activity index score and the C-reactive protein level was found in our study (r=0.302; p=0.001). The optimal C-reactive protein threshold value that separates patients with moderate to severe disease (Crohn's disease activity index>220) from the others was calculated to be 19mg/L with a sensitivity of 76.4% and a specificity of 56.2%. CONCLUSION: The C-reactive protein level is correlated to disease activity in Crohn's disease. Its role seems to be essential in predicting moderate and severe disease activity.

[A previously unreported late complication of Finney strictureplasty]. / Une complication tardive et inédite d'une stricturoplastie à la Finney.

We report the case of a 23 year old woman, treated for Crohn's disease for 11 years. She was operated on for multiple obstructing jejuno-ileal strictures using strictureplasty technique. Nine stricturoplasties of Heineke-Mikulicz type and one Finney type were performed without immediate postoperative complication. The patient received Imurel(R) and remained in remission for 15 months. Peritonitis due to a perforation of the Finney strictureplasty required re-operation; an ileostomy was performed. Such a late complication of a strictureplasty has not previously been reported in the literature. Although this complication was severe, the indication for this procedure in the surgical management of Crohn's complications should not be modified.